The present invention relates to a crystallization device used for making crystals in the liquid to liquid diffusion method. The liquid to liquid diffusion method is known as one of methods for protein crystallization. The liquid to liquid diffusion method is so operated that: protein solution and precipitant solution are in contact with each other to diffuse into each other at the free boundary between them; and the protein solution partly becomes a supersaturated condition so that the protein is crystallized. When performing experimentally screening of the conditions for the protein crystallization in the liquid to liquid diffusion method, it is preferable to perform experiments under many conditions at the same time with a small amount of a sample. A device suitable for such experiments is known as a crystallization plate which is disclosed in U.S. Patent Publication No. 2005/0201901 A1 which is referred to as the first publication hereinafter. The present invention relates to such a crystallization plate.
The crystallization plate in the first publication makes it possible to perform screening for many crystallization conditions at the same time with a small amount of a sample. The crystallization plate has many elongated channels inside which protein solution and precipitant solution are in contact with each other. The crystallization plate has three valves: an interface valve between a protein solution channel and a precipitant solution channel; a containment valve for protein solution supply disposed near a protein solution supply port; and another containment valve for precipitant solution supply disposed near a precipitant solution supply port. These valves are controlled to supply the protein solution and the precipitant solution and to launch counter diffusion between the protein solution and the precipitant solution. The valves are operated by a gas pressure and thus the crystallization plate requires a special device for the gas pressure. After the start of the diffusion, the interface valve is closed after the predetermined lapse of time, and then water vaporization from the protein solution goes underway to cause a variation in density of the protein solution, so that crystals are precipitated.
In addition, a gel counter diffusion method is known as one kind of the liquid to liquid diffusion method and is disclosed in J. Synchrotron Rad. (2004) 11, 45-48 “A simplified counter diffusion method combined with a 1-D simulation program for optimizing crystallization conditions” (the second publication) and Japanese Patent Publication No. 6-321700 A (1994) (the third publication). The gel counter diffusion method is so operated that: protein solution and precipitant solution are arranged with gel between them; and the protein solution and the precipitant solution diffuse into each other through the gel so that the protein is crystallized. The present invention relates to the gel counter diffusion method too.
The crystallization plate for the liquid to liquid diffusion method and the crystallization device for the gel counter diffusion method both have a problem in picking up grown crystals from the device. The conventional crystallization plate disclosed in the first publication also has a problem of requiring the special pressure device for pressure filling of the protein solution and the precipitant solution.